T Cell Transfer With or Without Dendritic Cell Vaccination in Patients With Melanoma

NCT01946373 | Unknown Phase 1 DMC

• 2 other identifiers: MAT-022012-000450-63
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn if dendritic cell vaccine will increase the effect of tumor infiltrating lymphocytes given with chemotherapy and interleukin-2 in patients with melanoma.

Conditions

Melanoma

Keywords

Melanoma; Dendritic cell vaccination; Lymphodepletion; Adoptive cell transfer; T cells; Tumor infiltrating lymphocytes; Fludarabine; IL-2; Interleukin-2; Cyclophosphamide; Phase I study; Monocytes; Autologous; NY-ESO-1

Outcome Measures

Primary Outcomes (1)

• Safety of the T cell therapy, with and without dendritic cell vaccine, as evaluated according to the NCI CTCAE scale version 4.0

  30 days

Secondary Outcomes (1)

• Time to disease progression assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

  4 weeks

Study Arms (2)

Chemotherapy + T cells + IL-2

EXPERIMENTAL

Cyclophosphamide 60 mg/kg/d by vein (IV) daily for 2 days followed by fludarabine 25 mg/m\^2 IV daily for 5 days before T cell infusion. The day after chemotherapy up to 5 x 10\^10 T cells IV infusion. Interleukin-2 90 minutes after T cell infusion at a dose of 100,000 IU/kg as IV bolus over 15 minute period every 8-hours for up to 14 doses.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: T cells; Biological: Interleukin-2

Chemotherapy + T cells + IL-2 + DCV

EXPERIMENTAL

Cyclophosphamide 60 mg/kg/d by vein (IV) daily for 2 days followed by fludarabine 25 mg/m\^2 IV daily for 5 days before T cell infusion. The day after chemotherapy up to 5 x 10\^10 T cells IV infusion. Interleukin-2 90 minutes after T cell infusion at a dose of 100,000 IU/kg as IV bolus over 15 minute period every 8-hours for up to 14 doses. After completion of the IL-2 treatment 3-5 doses of weekly intradermal vaccinations with up to 1.5 x 10\^7 Dendritic cells pulsed with autologous tumor lysate and NY-ESO-1 peptide.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: T cells; Biological: Interleukin-2; Biological: Dendritic cell vaccine

Interventions

Cyclophosphamide DRUG

Also known as: Sendoxan, Cytoxan, Neosar

Chemotherapy + T cells + IL-2; Chemotherapy + T cells + IL-2 + DCV

Fludarabine DRUG

Also known as: Fludarabine phosphate, Fludara

Chemotherapy + T cells + IL-2; Chemotherapy + T cells + IL-2 + DCV

T cells BIOLOGICAL

Chemotherapy + T cells + IL-2; Chemotherapy + T cells + IL-2 + DCV

Interleukin-2 BIOLOGICAL

Also known as: IL-2, Proleukin

Chemotherapy + T cells + IL-2; Chemotherapy + T cells + IL-2 + DCV

Dendritic cell vaccine BIOLOGICAL

Chemotherapy + T cells + IL-2 + DCV

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with measurable (direct on body surface or by x-ray and/or CT) malignant melanoma (including uveal melanoma), that is advanced, inoperable stage III (advanced regional lymph node metastases, or more than 5 in-transit metastases, N2) or stage IV (distant metastasis, M1) according to the AJCC classification and confirmed by histology/cytology and appropriate radiological investigations.
• Patients with a palpable resectable lesion located in the skin or in a lymph node or a lesion accessible by (core) biopsy.
• Disease should be in progression and the patient should have exhausted other approved therapeutic options, if not the physician considers that an earlier study entry benefits the patient.
• Ambulatory performance status (ECOG 0, 1, 2).
• Age 18-74 and life expectancy greater than 3 months.

You may not qualify if:

• Any of the above criteria are not met.
• Significant history or current evidence of cardiovascular disease (e.g. uncontrolled congestive heart failure or hypertension, unstable coronary artery disease or serious arrhythmias) or major respiratory diseases. In questionable cases, a stress test should be performed.
• Other serious illnesses, e.g. active infections requiring antibiotics, bleeding disorders.
• Has had prior systemic cancer therapy within the past four weeks at the time of the start of the lymphodepletion regimen.
• Patients diagnosed with prior malignancies (except adequately treated basal cell carcinomas of the skin or in situ carcinomas of the skin or in situ carcinomas of the cervix, surgically cured) within the past 5 years.
• Patients with second advanced malignancies concurrently.
• Active CNS metastases. (Note: Patients with brain metastases that have been completely resected at least one month prior to registration or have undergone gamma knife treatment with no evidence of recurrence on CT and who are neurologically stable, are not excluded).
• Organic brain syndrome or significant psychiatric disorder which would preclude participation in the full protocol and follow-up.
• Immunodeficiency, previous splenectomy or radiation therapy of the spleen.
• Screening laboratory values:
• a) Inadequate hematologic function defined by: i) White blood count (WBC) \<3.0 x 109/l ii) Platelet count \<100x109/l iii) Hemoglobin level \<100 g/l b) Inadequate hepatic function as defined by either: i) Total bilirubin level \>1.5 times the upper limit of normal (ULN) ii) Aspartate amino transferase (AST) or alanine amino transferase (ALT) \>3 times the ULN (if related to liver metastases \>5 times the ULN) c) Inadequate renal function defined as serum creatinine \>1.5 times the ULN
• Infectious diseases that can be transmitted via contact with blood, such as HIV, Hepatitis B and C.
• Women who are pregnant or nursing will be excluded because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

Sponsors & Collaborators

• Karolinska University Hospital: lead

Study Sites (1)

Karolinska University Hospital

Stockholm, SE-171 76, Sweden

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Maria Wolodarski, MD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Wolodarski, MD

CONTACT

+46851770000; maria.wolodarski@regionstockholm.se

Rolf Kiessling, MD, PhD

CONTACT

+46733428848; rolf.kiessling@ki.se

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: September 12, 2013
• First Posted: September 19, 2013
• Study Start: October 1, 2013
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: October 4, 2022

Record last verified: 2022-10

Locations

SE (1)